Behavior of beta-arrestin at the plasma membrane in the presence of a stimulated receptor. After spontaneous insertion into the plasma membrane (1), beta-arrestin reaches the receptor via lateral diffusion (2). Transient interaction with the receptor catalyzes beta-arrestin activation, including beta-arrestin inter-domain rotation and extension of the finger loop (3). Following dissociation from the receptor, the interaction of the extended finger loop with the lipid bilayer likely contributes to stabilizing beta-arrestin in a membrane-bound, active-like conformation (4). This causes beta-arrestin molecules to stay longer and accumulate on the plasma membrane, allowing them to reach CCPs vial lateral diffusion separately from the activating receptors (5). The increase in the number of active beta-arrestin molecules and time they spend diffusing on the plasma membrane leads their recruitment and accumulation in CCPs via interaction with AP2 and clathrin (6). beta-arrestin molecules tethered to CCPs bind receptors diffusing on the plasma membrane, also causing their recruitment and accumulation in CCPs (7).
